2629_Crowell-Davis_FM 8/8/05 9:07 AM Page i Veterinary Psychopharmacology 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page iii Veterinary Psychopharmacology by Sharon Crowell-Davis and Thomas Murray 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page iv © 2006 Blackwell Publishing All rights reserved Blackwell Publishing Professional 2121 State Avenue, Ames, Iowa 50014, USA Orders: 1-800-862-6657 Office: 1-515-292-0140 Fax: 1-515-292-3348 Web site: www.blackwellprofessional.com Blackwell Publishing Ltd 9600 Garsington Road, Oxford OX4 2DQ, UK Tel.: +44 (0)1865 776868 Blackwell Publishing Asia 550 Swanston Street, Carlton, Victoria 3053, Australia Tel.: +61 (0)3 8359 1011 Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Blackwell Publishing, provided that the base fee of $.10 per copy is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee codes for users of the Transactional Reporting Service are ISBN-13: 978-0-8138-0829-1; ISBN-10: 0-8138-0829-4/2005 $.10. First edition, 2006 Library of Congress Cataloging-in-Publication Data Crowell-Davis, Sharon L. Veterinary psychopharmacology / by Sharon Crowell-Davis and Thomas Murray.— 1st ed. p. cm. Includes bibliographical references. ISBN-13: 978-0-8138-0829-1 (alk. paper) ISBN-10: 0-8138-0829-4 (alk. paper) 1. Veterinary psychopharmacology. I. Murray, Thomas (Thomas F.) II. Title. SF756.84.C76 2005 636.089Ј578—dc22 2005012241 The last digit is the print number: 9 8 7 6 5 4 3 2 1 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page v Dedication For my father, Wallace Davis, whose lifelong dedication to science inspired me to fol- low in his footsteps, although on a very different path; my mother, Ruth Davis, who raised me to believe in myself; my husband, William Crowell-Davis, who has stood beside me through thick and thin; and for our two wonderful children, James Michael and Kristina Crowell-Davis, who grew up with a mother who always had animals around the house and was sometimes distracted by her work. Also for Prince, “the best dog in the history of the world,” and my childhood friend, who no doubt initiated my love of animals. Sharon Crowell-Davis 2005 To my wife, Cristina Wojcik, and daughter, Lia Lorraine Murray, for their patience with psychopharmacology during events such as a honeymoon and holiday vacation. Thomas Murray 2005 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page vii Contents Contributors ix Acknowledgments xi Preface xiii Chapter 1 Introduction 3 Chapter 2 Amino Acid Neurotransmitters: Glutamate, GABA, and the 25 Pharmacology of Benzodiazepines Chapter 3 Benzodiazepines 34 Chapter 4 Biogenic Amine Neurotransmitters: Serotonin 72 Chapter 5 Selective Serotonin Reuptake Inhibitors 80 Chapter 6 Azapirones 111 Chapter 7 Biogenic Amine Transmitters: Acetylcholine, 119 Norepinephrine, and Dopamine Chapter 8 Monoamine Oxidase Inhibitors 134 Chapter 9 Antipsychotics 148 Chapter 10 CNS Stimulants 166 Chapter 11 Tricyclic Antidepressants 179 Chapter 12 Endogenous Opioid Peptides 207 Chapter 13 Opioids and Opioid Antagonists 212 Chapter 14 Hormones 224 Chapter 15 Combinations 234 Appendix 241 Index 261 vii 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page ix Contributors Sharon L. Crowell-Davis, DVM, PhD (Chapters 1, 3, 5, 6, 8, 10, 11, 13–15) Diplomate, American College of Veterinary Behaviorists Professor of Veterinary Behavior The University of Georgia College of Veterinary Medicine Department of Anatomy and Radiology Vet Med 1 Athens, GA 30602 Thomas Murray, BS, PhD (Chapters 2, 4, 7, 12) Distinguished Research Professor and Head The University of Georgia College of Veterinary Medicine Department of Physiology and Pharmacology 2223A Vet Med 1 Athens, GA 30602 Lynne M. Seibert, BS, DVM, MS, PhD (Chapter 9) Diplomate, American College of Veterinary Behaviorists Veterinary Behavior Specialist VCA Veterinary Specialty Center 20115 - 44th Avenue West Lynnwood, WA 98036 ix 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page xi Acknowledgments First, I would like to thank the many veterinarians who called me with questions about psychoactive medications, because it was their calls that triggered the realization that the general practitioner needed a resource that helped them to arrive at good decisions about drug selection and to better understand the drugs they were using. Without their eagerness to gain knowledge in this field, this book would not have been written. Many people besides the authors contributed to the substantial work involved in bringing together the information presented in this first edition. Of particular assis- tance were Linda Tumlin, Wendy Simmons, and Lucy Rowland. In their capacity as librarians and reference librarians they were invaluable in locating and obtaining much of the information provided between these covers. Information on drug costs was obtained through the able assistance of the University of Georgia Behavior Service Technician, Melissa Christian, and Sharon Campany, Certified Pharmacy Technician. Students always challenge a professor to clarify and explain their decisions. In this context, the hundreds of veterinary students to whom I have taught the field of veteri- nary behavior over the last 27 years were significant contributors. Even more so were my first three residents, Dr. Lynne Seibert, an author in this book, Dr. Terry Curtis, and Dr. Mami Irimajiri. Drs. Seibert and Curtis also assisted in the teaching of our first continuing education course on psychopharmacology for veterinarians to graduate veterinarians. It was in the planning sessions for the organization of that course that much of the organization of this book developed. The course would not have taken place without the able assistance of Sandi Kilgo, who coordinated the details of the everyday running of the course. I could not have developed the behavior program and the behavior service at the University of Georgia to its current strength if I had not had the continuing support of various administrators over the years. Dr. Royce Roberts, my department head of many years, has been particularly helpful. Dr. David Anderson, Dr. Keith Prasse, Dr. Bob Lewis, and Dr. Jack Munnell have also facilitated my continuing work in this field. Sharon L. Crowell-Davis, 2005 xi 2629_Crowell-Davis_FM 8/8/05 9:07 AM Page xiii Preface This book grew out of a series of phone calls I received over the years from various veterinarians wanting information about their patients’ behavior problems and the psychoactive medications that might help them. What were appropriate drugs for given problems? What were appropriate doses? What side effects should be watched for? The first answer to this steadily accumulating set of questions was a continuing education course in psychopharmacology specifically organized for veterinarians. The course was first presented at the University of Georgia in November of 2001 and is now presented biannually. Dr. Murray and I co-taught the course, with assistance from the clinical residents in behavior at the time, Dr. Lynne Seibert and Dr. Terry Curtis. The approach of coverage of the basic science of the molecular activity of the brain, followed by coverage of clinical applications (i.e., what drugs have been used in vet- erinary patients to affect that particular molecular activity and how well have they worked to treat behavior problems), was well received. The logical next step was a textbook so that practicing veterinarians would have a resource to turn to for the an- swers to their various questions. Information on the effects of various psychoactive drugs in dogs, cats, and other veterinary patients comes from two major sources. First, animals were often used to test and study the actions of various drugs during their initial development. Thus, the reader who peruses the references will find papers published as early as the 1950s, when major breakthroughs in psychopharmacology were being made. The second set of information is much more recent. With the establishment of the American College of Veterinary Behaviorists in 1993 and the overall rapid development of the field of veterinary behavior over the last three decades, there has been increasing research on the efficacy of various medications on the treatment of various behavioral disorders of companion animals, zoo animals, and other nonhuman animals. There are often huge gaps in our knowledge, and the reader may note them through- out the book. While we can glean bits and pieces of pharmacokinetic and other data from studies done on dogs and cats during early drug development, the quality and quantity of the information is highly variable. Studies of teratology and carcinogenic- ity are typically done in rats, mice, and rabbits, while comprehensive studies of all as- pects of pharmacological activity in the body are done only in humans, the species that has historically been of interest. It is hoped that, as interest in this field continues to evolve, more comprehensive data will become available; new data will be supplied in future editions. Sharon Crowell-Davis, DVM, PhD Diplomate, American College of Veterinary Behaviorists Professor of Veterinary Behavior The University of Georgia xiii 2629_Crowell-Davis_Chap 01 8/8/05 9:09 AM Page 3 Chapter One Introduction The term psychopharmacology derives from three Greek words. Psyche means soul or mind. Pharmacon means drug. Finally, the term logos means to study. Thus, psy- chopharmacology, in a basic sense, is the study of drugs that affect the soul or mind. We are interested in such drugs because psychoactive medications produce changes in behavior and/or motivation. They have been used with varying efficacy in human psy- chiatry for several decades, and efficacy has improved over time as we have come to better understand the complex interrelationships between brain chemistry, internal emotional states, and overt behavior.